Both acute and chronic stress can have long-term physiological and psychological consequences, some of which can be ameliorated through positive social interaction. The current proposal will examine the effects of prior exposure to positive social interaction versus social stress on the histological, physiological and behavioral consequences of experimental stroke. In addition, alterations in the corticosteroid, glutamate and antioxidant responses to experimental stroke will be examined as possible mechanisms through which social cues can influence histological and functional outcome in this model. The data collected as part Of this proposal will increase our understanding of the basic pathophysiological mechanism of cerebral ischemia and the roles that social interaction and the hypothalamic-pituitary-adrenal axis play in modulating excitotoxic neuronal death. Ultimately, understanding the factors that modulate neurotoxicity and behavioral outcomes may facilitate the development of therapeutic approaches for the prevention and treatment of cerebral ischemia. Taken together, the proposed studies will provide a neurobiological foundation on which to study the effects of social cues on experimental stroke outcome, and may provide insights into the mechanisms underlying individual differences in outcome following an ischemic event.